Drug Shortage

Shortage of flumazenil for injection

3D model of flumazenil contributed to Wikimedia by Ccroberts

The American Society of Health-System Pharmacists reports a shortage of flumazenil for injection. This a drug you might inject into someone who enters your emergency department because of a life-threatenting benzodiazepine overdose. It might also be used to reverse the effects of midazolam, often used for short-term sedation. I personally have not seen flumazenil used this way in conjunction with midazolam, and there doesn’t seem to me to be any advantage since there must still be a postoperative waiting period for safety’s sake. It does seem reasonable that a doctor might want a patient to become much more alert after surgery in some instances, so perhaps that is when it is used. Using flumazenil can endanger patients who have taken BZDs over the long term, in the same fashion that abrupt discontinuation of the tablets can cause harm.

Fresenius-Kabi attributed this supply shortage to short-term manufacturing delays. “Sandoz and Mylan Institutional cannot provide a reason for the shortage.” West-Ward evidently didn’t respond to this query at all or perhaps just not in a timely manner.

I have my own reasonable hypothesis for the shortage of injectable flumazenil, based on a US population in which there is an ever-increasing number of elders. When Medicare began covering the cost of benzodiazepine prescriptions in 2013, it became immediately obvious that a staggering number of people had been prescribed BZDs over the long term, a prescribing practice which is now discouraged due to delirium, addiction, falls, and cognitive decline. The conclusion of a recent JAMA Psychiatry abstract (paywall) was:

Despite cautions concerning risks associated with long-term benzodiazepine use, especially in older patients, long-term benzodiazepine use remains common in this age group. More vigorous clinical interventions supporting judicious benzodiazepine use may be needed to decrease rates of long-term benzodiazepine use in older adults.

Exhibiting their bias, the above authors imply that this is due to patient demand, but the prescribing physicians don’t seem to be tapering the BZD doses, as would seem logical. Some of the data and a graph are brought out from behind JAMA’s paywall in this press release from the National Institute of Mental Health.

One of the study authors is quoted in this release from the American Psychiatric Association.

“It was alarming to find the highest rates of benzodiazepine use among the group with the highest risks,” said study author Michael Schoenbaum, Ph.D., of the Office of Science Policy, Planning, and Evaluation at the National Institute of Mental Health. “Given that safer, effective options are available for anxiety and insomnia, it’s hard to make a clinical argument for these results.”
“It may be time to act, perhaps first by restricting the prescription of benzodiazepines to psychiatrists. In the study, psychiatrists seemed to prescribe them properly. The next step is to consider them the same as other dangerous addictive substances and put them on a tight dispensation schedule using limited-duration prescriptions with no refills,” the commentary authors wrote.

It has not been my experience that psychiatrists prescribe benzodiazepines properly, although I am sure some do. You can check the prescribing habits of your physician here.

Here is a doctor’s blog post on this subject for your further reading: “Doctors of tomorrow: please forgive us for thinking that it was a great idea to prescribe sedatives, opiates and stimulants to just about everybody

In my experience in trying to deal with this situation, I have found some unexpected allies: the patients themselves. In every patient who I talk to about tapering off of controlled substances I expect anger and resistance. But this is not always the case. I have met patients who seemed like they had just been waiting for someone to help them get off of these meds. It’s not even all that uncommon. People don’t actually like to be passive and helpless and weak and sleepy and constipated, and some of them are willing to risk experiencing pain or other discomforts in trade for not being on drugs. I see patients on the other end of the process, too. They say that after their injury or operation they were heavily dependent on drugs and that they eventually got fed up and, with the help of a good doctor or nurse or family, got off of them and intend never to take them regularly again.

Dr. Boughton is a rarity. The prescribing practice of two groups of hospitalists who contract with St. David’s and Seton hospitals in Austin, Texas, has been poor in my experience. I have personally met one family practice doctor who follows the new prescribing guidelines for benzodiazepines.

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